ADAMs (a disintegrin and a metalloprotease) are a novel class of cell surface glycoproteins that exhibits both proteolytic and adhesive activities. The mechanisms of ADAMs in biological settings, in particular the interplay between their adhesive and proteolytic domains, remain unclear. Several lines of evidence suggest that ADAMs may function in cell migration, such as in cranial neural crest (CNC) migration. Due to their importance in the developing face and head, defects in CNC migration could result in craniofacial defects or lethality. An estimated one-third of human birth defects are attributed to aberrant craniofacial development. The goals of this project are to explore the roles of ADAMs in cell migration utilizing mouse CNC as a model system to establish which integrin(s) and which ADAM(s) participate in mouse CNC migration, and to determine if ADAMs function in cell migration through their adhesive and/or proteolytic domains. The proposed studies will not only provide further insight into CNC migration, but they will provide a framework for evaluating how ADAMs may function in other cell migration events including leukocyte transmigration, angiogenesis, and tumor cell metastasis.